申请人:Hoffman-La Roche Inc.
公开号:US04766133A1
公开(公告)日:1988-08-23
(Benzimidazol-2-yl)-pyridinium compounds of the formula ##STR1## wherein A is --SR.sup.9, --SO.sub.3.sup.- or --S--SO.sub.3.sup.- ; R.sup.1 and R.sup.3 each is hydrogen or (C.sub.1 -C.sub.7)-alkyl; R.sup.2 is hydrogen, (C.sub.1 -C.sub.7)-alkyl, (C.sub.1 -C.sub.7)-alkoxy or a negatively charged oxygen atom; R.sup.4 is hydrogen or a negative charge; R.sup.5, R.sup.6, R.sup.7 and R.sup.8 each is hydrogen, (C.sub.1 -C.sub.7)-alkyl, aryl, halogen, cyano, nitro, formyl, (C.sub.2 -C.sub.7)-alkanoyl, arylcarbonyl, carboxy, carboxy-(C.sub.1 -C.sub.7)-alkyl, (C.sub.1 -C.sub.7)-alkoxycarbonyl, aryloxycarbonyl, aryl-(C.sub.1 -C.sub.7)-alkoxycarbonyl, (C.sub.1 -C.sub.7)-alkoxycarbonyl-(C.sub.1 -C.sub.7)-alkyl, carbamoyl, mono- or di-(C.sub.1 -C.sub.7)-alkylcarbamoyl, pyrrolidinocarbonyl, piperidinocarbonyl, carbamoyl-(C.sub.1 -C.sub.7)-alkyl, mono- or di-(C.sub.1 -C.sub.7)-alkylcarbamoyl-(C.sub.1 -C.sub.7)-alkyl, pyrrolidinocarbonyl-(C.sub.1 -C.sub.7)-alkyl, piperdinocarbonyl-(C.sub.1 -C.sub.7)-alkyl, hydroxy, (C.sub.1 -C.sub.7)-alkoxy, (C.sub.2 -C.sub.7)-alkanoloxy, aryloxy, arylcarbonyloxy, (C.sub.1 -C.sub.7)-alkoxycarbonyloxy, aryl-(C.sub.1 -C.sub.7)-alkoxycarbonyloxy, aryloxycarbonyloxy, carbamoyloxy, mono- or di-(C.sub.1 -C.sub.7)-alkylcarbamoyloxy, pyrrolidinocarbonyloxy, piperidinocarbonyloxy, hydroxy-(C.sub.1 -C.sub.7)-alkyl, trifluoromethyl, di-(C.sub.1 -C.sub.7)-alkoxymethyl or (C.sub.2 -C.sub.3)-alkylenedioxymethyl or two of these substituents which are adjacent jointly and together with the carbon atoms to which they are attached are a 5-, 6- or 7-membered ring; and R.sup.9 is (C.sub.1 -C.sub.20)-alkyl, (C.sub.3 -C.sub.7)-cycloalkyl, (C.sub.3 -C.sub.7)-alkenylalkyl, (C.sub.3 -C.sub.7)-alkynylalkyl, substituted (C.sub.3 -C.sub.7)- alkenyl-alkyl, aryl, aryl-(C.sub.1 -C.sub.7)-alkyl, hydroxy- (C.sub.2 -C.sub.7)-alkyl, (C.sub.1 -C.sub.7)-alkoxy- (C.sub.2 -C.sub.7)-alkyl, (C.sub.1 -C.sub.7)-alkoxycarbonyl- (C.sub.1 -C.sub.7)-alkyl, carboxy-(C.sub.1 -C.sub.7)-alkyl, di-(C.sub.1 -C.sub.7)-alkoxycarbonyl-(C.sub.2 -C.sub.7)-alkyl, dicarboxy-(C.sub.2 -C.sub.7)-alkyl, carboxy-(C.sub.1 -C.sub.7)-alkylcarbamoyl-(C.sub.1 -C.sub.7)-alkyl, optionally N-substituted amino-(C.sub.2 -C.sub.7)-alkyl, optionally N-substituted amino-carboxy-(C.sub.2 -C.sub.7)-alkyl, optionally N-substituted amino-(C.sub.1 -C.sub.7)-alkoxycarbonyl-(C.sub.2 -C.sub.7)-alkyl, heteroaryl, heteroaryl-(C.sub.1 -C.sub.7)-alkyl or a residue derived from a cysteine-containing oligopeptide by elimination of the SH group; provided that when there is a net single positive charge there is an external anion, or a pharmaceutically acceptable acid addition salt thereof.
苯并咪唑-2-基吡啶化合物的化学式为##STR1##其中A为--SR.sup.9,--SO.sub.3.sup.-或--S--SO.sub.3.sup.-;R.sup.1和R.sup.3分别为氢或(C.sub.1 -C.sub.7)-烷基;R.sup.2为氢,(C.sub.1 -C.sub.7)-烷基,(C.sub.1 -C.sub.7)-烷氧基或带负电荷的氧原子;R.sup.4为氢或带负电荷;R.sup.5,R.sup.6,R.sup.7和R.sup.8分别为氢,(C.sub.1 -C.sub.7)-烷基,芳基,卤素,氰基,硝基,甲酰基,(C.sub.2 -C.sub.7)-烷酰基,芳基羰基,羧基,羧基-(C.sub.1 -C.sub.7)-烷基,(C.sub.1 -C.sub.7)-烷氧羰基,芳氧羰基,芳基-(C.sub.1 -C.sub.7)-烷氧羰基,(C.sub.1 -C.sub.7)-烷氧羰基-(C.sub.1 -C.sub.7)-烷基,氨基甲酰基,单或双-(C.sub.1 -C.sub.7)-烷基氨基甲酰基,吡咯烷甲酰基,哌啶甲酰基,氨基甲酰基-(C.sub.1 -C.sub.7)-烷基,单或双-(C.sub.1 -C.sub.7)-烷基氨基甲酰基-(C.sub.1 -C.sub.7)-烷基,吡咯烷甲酰基-(C.sub.1 -C.sub.7)-烷基,哌啶甲酰基-(C.sub.1 -C.sub.7)-烷基,羟基,(C.sub.1 -C.sub.7)-烷氧基,(C.sub.2 -C.sub.7)-烷氧基,芳氧基,芳基羰氧基,(C.sub.1 -C.sub.7)-烷氧羰氧基,芳基-(C.sub.1 -C.sub.7)-烷氧羰氧基,芳氧羰氧基,氨基氧基,单或双-(C.sub.1 -C.sub.7)-烷基氨基氧基,吡咯烷甲酰氧基,哌啶甲酰氧基,羟基-(C.sub.1 -C.sub.7)-烷基,三氟甲基,双-(C.sub.1 -C.sub.7)-烷氧甲基或(C.sub.2 -C.sub.3)-烷二氧甲基或其中两个相邻的这些取代基与它们连接的碳原子一起形成5、6或7元环;R.sup.9为(C.sub.1 -C.sub.20)-烷基,(C.sub.3 -C.sub.7)-环烷基,(C.sub.3 -C.sub.7)-烯基烷基,(C.sub.3 -C.sub.7)-炔基烷基,取代的(C.sub.3 -C.sub.7)-烯基-烷基,芳基,芳基-(C.sub.1 -C.sub.7)-烷基,羟基-(C.sub.2 -C.sub.7)-烷基,(C.sub.1 -C.sub.7)-烷氧基-(C.sub.2 -C.sub.7)-烷基,(C.sub.1 -C.sub.7)-烷氧羰基-(C.sub.1 -C.sub.7)-烷基,羧基-(C.sub.1 -C.sub.7)-烷基,双-(C.sub.1 -C.sub.7)-烷氧羰基-(C.sub.2 -C.sub.7)-烷基,二羧基-(C.sub.2 -C.sub.7)-烷基,羧基-(C.sub.1 -C.sub.7)-烷基氨基甲酰基-(C.sub.1 -C.sub.7)-烷基,可选地N-取代氨基-(C.sub.2 -C.sub.7)-烷基,可选地N-取代氨基-羧基-(C.sub.2 -C.sub.7)-烷基,可选地N-取代氨基-(C.sub.1 -C.sub.7)-烷氧羰基-(C.sub.2 -C.sub.7)-烷基,杂环芳基,杂环芳基-(C.sub.1 -C.sub.7)-烷基或通过消除-SH基而得到的半胱氨酸寡肽的残基;但当存在净正电荷时,存在外部阴离子,或其药用可接受酸盐。